Abstract
In this report, we establish that Drosophila ADAR (adenosine deaminase acting on RNA) forms a dimer on double-stranded (ds) RNA, a process essential for editing activity. The minimum region required for dimerization is the N-terminus and dsRNA-binding domain I (dsRBD1). Single point mutations within dsRBD1 abolish RNA-binding activity and dimer formation. These mutations and glycerol gradient analysis indicate that binding to dsRNA is important for dimerization. However, dimerization can be uncoupled from dsRNA-binding activity, as a deletion of the N-terminus (amino acids 1-46) yields a monomeric ADAR that retains the ability to bind dsRNA but is inactive in an editing assay, demonstrating that ADAR is only active as a dimer. Different isoforms of ADAR with different editing activities can form heterodimers and this can have a significant effect on editing in vitro as well as in vivo. We propose a model for ADAR dimerization whereby ADAR monomers first contact dsRNA; however, it is only when the second monomer binds and a dimer is formed that deamination occurs.
Original language | English |
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Pages (from-to) | 3421-3430 |
Number of pages | 10 |
Journal | EMBO Journal |
Volume | 22 |
Issue number | 13 |
DOIs | |
Publication status | Published - Jul 1 2003 |
Keywords
- ADAR
- Dimer
- Drosophila
- Ion channels
- RNA editing
ASJC Scopus subject areas
- Genetics
- Cell Biology